Amplifying T cell‐mediated antitumor immune responses in nonsmall cell lung cancer through photodynamic therapy and anti‐PD1

• Published in: Cell biochemistry and function Vol. 42; no. 1; pp. e3925 - n/a
• Main Authors: Gong, Beilei, Wang, Liping, Zhang, Han, Wang, Qingkai, Li, Wei
• Format: Journal Article
• Language: English
• Published: England Wiley Subscription Services, Inc 01.01.2024
• Subjects: 1-Phosphatidylinositol 3-kinase; 5-Aminolevulinate Synthetase; ADAM12; Adenocarcinoma; AKT protein; ALAS2; Animals; Anticancer properties; Antitumor activity; Apoptosis; Carcinoma, Non-Small-Cell Lung - drug therapy; CD8 antigen; CD8-Positive T-Lymphocytes; Cell death; Effectiveness; Encyclopedias; Epidermal growth factor receptors; ErbB Receptors; Forkhead Transcription Factors; Foxp3 protein; Gene expression; Genes; Genomes; Humans; immune cell infiltration; Immunity; Immunofluorescence; Immunotherapy; Infiltration; ITGA10; Lung cancer; Lung carcinoma; Lung Neoplasms - drug therapy; Lymphocytes; Lymphocytes T; Macrophages; Malignancy; Metalloproteinase; Metastases; Mice; Mice, Inbred C57BL; Non-small cell lung carcinoma; PD-1 protein; Phosphatidylinositol 3-Kinases; Photochemotherapy; Photodynamic therapy; Polymerase chain reaction; Proteins; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; transcriptome analysis; Tumors; Xenotransplantation; ALAS2; immune cell infiltration; transcriptome analysis; ITGA10; ADAM12
• ISSN: 0263-6484; 1099-0844; 1099-0844
• DOI: 10.1002/cbf.3925

Photodynamic therapy (PDT) is nowadays widely employed in cancer treatment. We sought to assess the efficacy of combining PDT with anti‐programmed cell death protein 1 (PD1) and to investigate the associated mechanisms in nonsmall cell lung cancer (NSCLC). We established a xenograft tumor model in C57BL/6J mice using Lewis lung carcinoma (LLC) cells, recorded tumor growth, and quantified reactive oxygen species (ROS) levels using a ROS detection kit. Pathological changes were assessed through H&E staining, while immunofluorescence (IF) was used to determine the expression of CD8 and Foxp3. Transcriptomic analysis was conducted, analyzing differential expressed genes (DEGs) among control, PDT, and PDT combined with anti‐PD1 (PDT+anti‐PD1) groups. Functional enrichment analysis via Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) was performed. The Cancer Genome Atlas (TCGA) database was utilized to analyze the expression of aminolevulinate synthase gene (ALAS2), integrin alpha10 (ITGA10), ATP1A2, a disintegrin and metalloprotease 12 (ADAM12), and Lox1 in lung adenocarcinoma and adjacent tissues, with concurrent immune infiltration analysis. Quantitative real‐time polymerase chain reaction and western blot were employed to measure mRNA and protein expression levels. Treatment with PDT combined with anti‐PD1 significantly inhibited tumor growth and increased the number of CD8+ cells while decreasing Foxp3+ cells. Immune infiltration results presented ALAS2, ADAM12, and ITGA10 were associated with various types of T cells or macrophages. Additionally, the expression levels of EGFR, ERK, and PI3K/Akt were suppressed after PDT with anti‐PD1 treatment. Our findings collectively suggest that PDT combined with anti‐PD1 treatment could enhance the infiltration of CD8+ T cells, suppressing tumor growth, and this effect was associated with ALAS2, ITGA10, and ADAM12. The underlying mechanism might be linked to EGFR, ERK, and PI3K/Akt signaling. Overall, this study provides valuable insights into the application of PDT combined with anti‐PD1 treatment in NSCLC. Significance statement Photodynamic therapy (PDT) is a physical modality with promising therapeutic applications. Owing to its tumor site selectivity and minimal adverse effects, PDT has been utilized for treating various solid malignancies. We investigated the efficacy of combined PDT and anti‐PD1 immunotherapy on tumor progression. Our findings demonstrate that the combination of PDT and anti‐PD1 exhibits potent antitumor activity against nonsmall cell lung cancer (NSCLC). The underlying mechanism appears to involve increased tumor‐infiltrating CD8+ T cells.